The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease
Abstract We have previously identified a network of higher-order brain regions particularly vulnerable to the ageing process, schizophrenia and Alzheimer’s disease. However, it remains unknown what the genetic influences on this fragile brain network are, and whether it can be altered by the most co...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46344-2 |
| _version_ | 1797233498763821056 |
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| author | Jordi Manuello Joosung Min Paul McCarthy Fidel Alfaro-Almagro Soojin Lee Stephen Smith Lloyd T. Elliott Anderson M. Winkler Gwenaëlle Douaud |
| author_facet | Jordi Manuello Joosung Min Paul McCarthy Fidel Alfaro-Almagro Soojin Lee Stephen Smith Lloyd T. Elliott Anderson M. Winkler Gwenaëlle Douaud |
| author_sort | Jordi Manuello |
| collection | DOAJ |
| description | Abstract We have previously identified a network of higher-order brain regions particularly vulnerable to the ageing process, schizophrenia and Alzheimer’s disease. However, it remains unknown what the genetic influences on this fragile brain network are, and whether it can be altered by the most common modifiable risk factors for dementia. Here, in ~40,000 UK Biobank participants, we first show significant genome-wide associations between this brain network and seven genetic clusters implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s disease, and with the two antigens of the XG blood group located in the pseudoautosomal region of the sex chromosomes. We further reveal that the most deleterious modifiable risk factors for this vulnerable brain network are diabetes, nitrogen dioxide – a proxy for traffic-related air pollution – and alcohol intake frequency. The extent of these associations was uncovered by examining these modifiable risk factors in a single model to assess the unique contribution of each on the vulnerable brain network, above and beyond the dominating effects of age and sex. These results provide a comprehensive picture of the role played by genetic and modifiable risk factors on these fragile parts of the brain. |
| first_indexed | 2024-04-24T16:17:08Z |
| format | Article |
| id | doaj.art-f392aeae61674a35ae9159c1f37dfbd2 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T16:17:08Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-f392aeae61674a35ae9159c1f37dfbd22024-03-31T11:26:32ZengNature PortfolioNature Communications2041-17232024-03-0115111110.1038/s41467-024-46344-2The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and diseaseJordi Manuello0Joosung Min1Paul McCarthy2Fidel Alfaro-Almagro3Soojin Lee4Stephen Smith5Lloyd T. Elliott6Anderson M. Winkler7Gwenaëlle Douaud8FMRIB Centre, Wellcome Centre for Integrative Neuroimaging (WIN), Nuffield Department of Clinical Neurosciences, University of OxfordDepartment of Statistics and Actuarial Science, Simon Fraser UniversityFMRIB Centre, Wellcome Centre for Integrative Neuroimaging (WIN), Nuffield Department of Clinical Neurosciences, University of OxfordFMRIB Centre, Wellcome Centre for Integrative Neuroimaging (WIN), Nuffield Department of Clinical Neurosciences, University of OxfordFMRIB Centre, Wellcome Centre for Integrative Neuroimaging (WIN), Nuffield Department of Clinical Neurosciences, University of OxfordFMRIB Centre, Wellcome Centre for Integrative Neuroimaging (WIN), Nuffield Department of Clinical Neurosciences, University of OxfordDepartment of Statistics and Actuarial Science, Simon Fraser UniversityNational Institutes of Mental Health, National Institutes of HealthFMRIB Centre, Wellcome Centre for Integrative Neuroimaging (WIN), Nuffield Department of Clinical Neurosciences, University of OxfordAbstract We have previously identified a network of higher-order brain regions particularly vulnerable to the ageing process, schizophrenia and Alzheimer’s disease. However, it remains unknown what the genetic influences on this fragile brain network are, and whether it can be altered by the most common modifiable risk factors for dementia. Here, in ~40,000 UK Biobank participants, we first show significant genome-wide associations between this brain network and seven genetic clusters implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s disease, and with the two antigens of the XG blood group located in the pseudoautosomal region of the sex chromosomes. We further reveal that the most deleterious modifiable risk factors for this vulnerable brain network are diabetes, nitrogen dioxide – a proxy for traffic-related air pollution – and alcohol intake frequency. The extent of these associations was uncovered by examining these modifiable risk factors in a single model to assess the unique contribution of each on the vulnerable brain network, above and beyond the dominating effects of age and sex. These results provide a comprehensive picture of the role played by genetic and modifiable risk factors on these fragile parts of the brain.https://doi.org/10.1038/s41467-024-46344-2 |
| spellingShingle | Jordi Manuello Joosung Min Paul McCarthy Fidel Alfaro-Almagro Soojin Lee Stephen Smith Lloyd T. Elliott Anderson M. Winkler Gwenaëlle Douaud The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease Nature Communications |
| title | The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease |
| title_full | The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease |
| title_fullStr | The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease |
| title_full_unstemmed | The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease |
| title_short | The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease |
| title_sort | effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease |
| url | https://doi.org/10.1038/s41467-024-46344-2 |
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